The focus of this investigation has been to evaluate how cancer may effect the antitumor functions of human monocytes. Our initial studies revealed that monocytes from untreated patients with a variety of neoplasms including lymphoma, breast cancer, and colon carcinoma were able to recognize and kill malignant tumor cells in vitro in a comparable manner to monocytes from normal healthy individuals. In addition, we were unable to detect any soluble circulating factors capable of influencing monocyte cytotoxic function from these patients. We also observed that we could augment monocyte tumoricidal function in vitro by pretreatment of monocytes from normal donors with several biological response modifiers, including the interferons (IFNs) and IFN reducers. Our most recent efforts have led to the observation that monocytes from untreated cancer patients are not refractory to the modulating effect of the IFNs and, thus, we have been unable to detect any impairment of in vitro antitumor function of human monocytes from cancer patients. We are currently investigating the biochemical events mediated by the IFNs on monocyte tumoricidal function. Our initial observations have indicated potent intracellular changes in several nucleotide processing enzymes occur following cell exposure to the IFNs in both monocytes and natural killer cells. We are now correlating these changes with tumor cell cytotoxicity. This should provide new insights into the efficacy of IFN therapy in cancer. (SR)